Whipple's disease: comparison of histology with diagnosis based on polymerase chain reaction in four consecutive cases.

Müller, Christian; Petermann, Dagmar; Stain, Christoph; Riemer, H.; Vogelsang, Harald; Schnider, Peter; Zeiler, K; Wrba, Fritz

doi:10.1136/gut.40.3.425

Cited by 40 publications

(29 citation statements)

References 15 publications

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“…Thus, the sensitivity of our stool PCR is 100% if compared to PCR from duodenal biopsies (Table 3). However, the clinical sensitivity, i.e., the sensitivity with regard to the detection of patients with Whipple's disease, is only 63% but still significantly higher than that of histopathology (4,17,19,23), with a clinical sensitivity of only 12.5% in our small series. This confirms that PCR from duodenal biopsies and stool specimens is significantly more sensitive than histopathology and that a number of patients with Whipple's disease show no gastrointestinal evidence (clinical or laboratory) whatsoever for the presence of this disease (9,11,20).…”

Section: Discussionmentioning

confidence: 47%

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

2002

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Whipple's disease is a rare multisystemic bacterial infection with variable clinical manifestations. For decades, the laboratory diagnosis was based on the demonstration of periodic acid Schiff-positive inclusions in macrophages of gastrointestinal biopsies. PCR has improved the diagnosis of Whipple's disease due to its increased sensitivity compared to histopathological analysis. To avoid invasive procedures for taking specimens, we have investigated the possibility of detecting Tropheryma whipplei DNA in feces rather than in biopsies or gastric aspirate of patients with and without Whipple's disease. Total bacterial DNA was isolated from stool specimens using Qiagen columns followed by a T. whipplei-specific hybridization step with a biotinylated capture probe and streptavidin-coated magnetic particles. The captured DNA was then amplified using the same seminested PCR targeting the 16S rRNA gene of the organism that had been applied to other specimens without capturing. For five of eight patients with Whipple's disease, duodenal biopsies and stool samples were PCR positive, whereas for the three other patients, both specimens were PCR negative. Of 84 patients without Whipple's disease, 75 tested negative in the duodenal biopsy and in the stool sample. For four, both specimens were positive. Five patients tested positive in the stool sample but not in the biopsy. However, for three of these five patients, the gastric aspirate had been PCR positive, indicating that the stool PCR result was true rather than false positive. Compared to PCR from duodenal biopsies, stool PCR has a sensitivity of 100% and a specificity of 97.3%. Additionally, 15 PCR-positive and 22 PCR-negative stool samples were extracted using the Invisorb Spin Stool DNA kit. The simplified stool extraction showed 93.3% sensitivity and 95.5% specificity compared to the target capture method. We conclude that PCR with stool specimens with either extraction method is a sensitive and specific diagnostic tool for the detection of T. whipplei DNA and one not requiring invasive sampling procedures.

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Section: Discussionmentioning

confidence: 47%

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

2002

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“…Detection of "T. whippelii" by PCR is routinely done by using DNA extracts from tissues or fluids of affected sites (gastrointestinal tract, joint, cardiovascular system, and CNS). The suggestion that PCRbased diagnosis of Whipple's disease may be possibly exclusively by using DNA extracted from blood (106,107,134) has been questioned (118,133). For example, Marth et al (118) did not find any evidence for "T. whippelii" DNA in peripheral blood mononuclear cells in four patients with active Whipple's disease (confirmed by PAS-positive intestinal biopsy specimens) or in four patients with treated inactive disease (PASnegative biopsy specimens) and five controls.…”

Section: Laboratory Diagnosismentioning

confidence: 98%

“…After initiation of antibiotic therapy, the clinical manifestations usually improve within a few weeks. At the same time, positive PCR results may become negative, suggesting an efficacy of the antibiotic treatment (22,133,148,150). However, the regression of histopathological findings is slower, and PAS-positive structures may persist for years.…”

Section: Treatmentmentioning

confidence: 99%

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Whipple's Disease and “Tropheryma whippelii”

2001

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SUMMARY Whipple's disease is a rare bacterial infection that may involve any organ system in the body. It occurs primarily in Caucasian males older than 40 years. The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifestations, and these signs may occur in the absence of gastrointestinal manifestations. Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared. Trimethoprim-sulfamethoxazole for at least 1 year is usually considered adequate to eradicate the infection. The microbiological diagnosis of this insidious disease is rendered difficult by the virtual lack of culture and serodiagnostic methods. It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy. Recently, the Whipple bacteria have been characterized at the molecular level by amplification of their 16S rRNA gene(s). Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli.” Based on its unique 16S ribosomal DNA (rDNA) sequence, species-specific primers were selected for the detection of the organism in clinical specimens by PCR. This technique is currently used as one of the standard methods for establishing the diagnosis of Whipple's disease. Specific and broad-spectrum PCR amplifications mainly but not exclusively from extraintestinal specimens have significantly improved diagnosis, being more sensitive than histopathologic analysis. However, “T. whippelii” DNA has also been found in persons without clinical and histological evidence of Whipple's disease. It is unclear whether these patients are true asymptomatic carriers or whether differences in virulence exist among strains of “T. whippelii” that might account for the variable clinical manifestations. So far, six different “T. whippelii” subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen “T. whippelii” as well as the host immune response are needed to fully understand this fascinating disease. The recent cultivation of the organisms is a promising major step in this direction.

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“…firmed by direct sequencing (13,17). For quantitation of T. whipplei genomes, a real-time PCR using the primers TW13F and TW163R (sequences kindly provided by B. LaScola, Marseille) was established, with a sensitivity of 5,000 genomes/ml sample volume (5).…”

mentioning

confidence: 99%

Tropheryma whipplei in the Environment: Survey of Sewage Plant Influxes and Sewage Plant Workers

Schöniger–Hekele

Petermann

Weber

et al. 2007

Appl Environ Microbiol

151

101

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Whipple's disease: comparison of histology with diagnosis based on polymerase chain reaction in four consecutive cases.

Abstract: Background-Polymerase chain reaction (PCR) based detection of species specific sequences of the 16S rRNA gene of Tro-

Cited by 40 publications

References 15 publications

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

Detection of Tropheryma whipplei DNA in Feces by PCR Using a Target Capture Method

Whipple's Disease and “Tropheryma whippelii”

Tropheryma whipplei in the Environment: Survey of Sewage Plant Influxes and Sewage Plant Workers

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